The oxyalkylene-containing compound of this invention, butyric acid, butyric acid salts, and the butyric acid derivatives of this invention are used for treating, preventing or ameliorating cancer and other proliferative diseases as well as for inducing wound healing, treating cutaneous ulcers, treating gastrointestinal disorders, treating blood disorders such as anemias, immunomodulation, enhancing recombinant gene expression, treating insulin-dependent patients, treating cystic fibrosis patients, inhibiting telomerase activity, treating virus-associated tumors, especially EBV-associated tumors, modulating gene expression and particularly augmenting expression of tumor suppressor genes, inducing tolerance to antigens, treating, preventing or ameliorating protozoan infection or inhibiting histone deacetylase in cells.
A method of potentiating the activities of the above compounds has been sought, particularly because some of these compounds exhibit short in vivo half-lives. One such method is to inhibit metabolism of these compounds by inhibiting the cellular .beta.-oxidation cycle. Such inhibition would appear to prolong the half-life of the compounds in a patient or in cells and hence increase the duration of therapeutic effectiveness of the compounds. Alternatively, the dosages needed to obtain equivalent therapeutic effects can be lowered.
Several drugs have been shown to decrease mitochondrial .beta.-oxidation of fatty acids, such as ibuprofen (Freneaux, et al., 1990, J. Pharmacol. Exp. Ther., 255:529-535), amineptine (Ramain, et al., 1981, Gastroenterol. Clin. Biol., 5:469-471; Le Dinh, et al., 1988, J. Pharmacol. Exp. Ther., 247:745-750), tianeptine (Fromenty, et al., 1989, Biochem. Pharmacol., 38:3743-3751), amiodarone (Fromenty, et al., 1990, Biochem. Pharmacol., 255:1377-1384), tetracycline (Zimmerman, et al., 1988, Hepatology, 8:1056-1062), and valproic acid and salicylic acid (Deschamps, et al., 1991, J. Pharmacol. Exp. Ther., 259:894-904). Many of the aforementioned drugs are non-steroidal antiinflammatory drugs (NSAIDs) These and those other compounds with substantially the same activity are termed .beta.-oxidation inhibitors herein.